There is truly only one way to reverse this problem – if it truly is a problem for you. I was frustrated that whenever I’d receive an alert from iCal, I’d get a popup that would then proceed to open Mac Mail, which I don’t use.
This is a nasty workaround, but basically sets a permission on the Mail application so that it is no longer readable or executable.
Firstly, to turn off the Mail notifications:
sudo chmod 000 /Applications/Mail.app/Contents/MacOS/Mail
Secondly, to re-enable:
sudo chmod 755 /Applications/Mail.app/Contents/MacOS/Mail